Intravenous allopurinol decreases myocardial oxygen consumption and increases mechanical efficiency in dogs with pacing-induced heart failure

Allopurinol, an inhibitor of xanthine oxidase, increases myofilament calciu m responsiveness and blunts calcium cycling in isolated cardiac muscle. We sought to extend these observations to conscious dogs with and without paci ng-induced heart failure and tested the prediction that allopurinol would h ave a positive inotropic effect without increasing energy expenditure, ther eby increasing mechanical efficiency. In control dogs (n=10), allopurinol ( 200 mg TV) caused a small positive inotropic effect, (dP/dt)(max) increased from 3103+/-162 to 3373+/-225 mm Hg/s (+8.3+/-3.2%; P=0.01), but preload-r ecruitable stroke work and ventricular elastance did not change. In heart f ailure (n=5), this effect was larger; (dP/dt)(max) rose from 1602+/-190 to 1988+/-251 mm Hg/s (+24.4+/-8.7%; P=0.03), preload-recruitable stroke work increased from 55.8+/-9.1 to 84.9+/-12.2 mm Hg (+28.1+/-5.3%; P=0.02), and ventricular elastance rose from 6.0+/-1.6 to 10.5+/-2.2 mm Hg/mm (P=0.03). Allopurinol did not affect myocardial lusitropic properties either in contr ol or heart failure dogs. In heart failure dogs, but not controls, allopuri nol decreased myocardial oxygen consumption (-49+/-4.6%; P=0.002) and subst antially increased mechanical efficiency (stroke work/myocardial oxygen con sumption; +122+/-42%; P=0.04). Moreover, xanthine oxidase activity was appr oximate to 4-fold increased in failing versus control dog hearts (387+/-125 versus 78+/-72 pmol/min.mg(-1); P=0.04) but was not detectable in plasma. These data indicate that allopurinol possesses unique inotropic properties, increasing myocardial contractility while simultaneously reducing cardiac energy requirements. The resultant boost in myocardial contractile efficien cy may prove beneficial in the treatment of congestive heart failure.